Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

3D model of human epidermis exposed to Staphylococci reveals keratinocyte responses unique to atopy-associated S. aureus challenge.

ABSTRACT: The interplay between microbiota and skin cells is a key factor underlying the pathophysiology of this barrier organ. Keratinocytes, the main components of the epidermis, are crucial for skin barrier function, but their responses to different bacteria are not well understood. We present a high-throughput analysis of the transcriptome of human epidermal-like organoids exposed to two vastly different bacterial skin colonists: Staphylococcus epidermidis and Staphylococcus aureus, which are commonly associated with mostly positive and negative interactions with the host, respectively. We observed partly overlapping but predominantly divergent epidermal changes in response to both bacteria. Among the genes most affected by S. aureus, those related to lipid metabolism were predominant. This work was supported by grants from the Polish National Science Center (UMO-2014/12/W/NZ6/00454 and 2019/35/B/NZ6/03357) and by a grant for research projects for Young Scientists and PhD students from the Jagiellonian University (N19/MNS/000020). The open-access publication has been supported by the Faculty of Biochemistry, Biophysics and Biotechnology under the Strategic Programme Excellence Initiative at Jagiellonian University in Krakow, Poland.

ORGANISM(S): Homo sapiens

PROVIDER: GSE276844 | GEO | 2025/03/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Adverse Events of anti-EGFR Therapy are Triggered by Hair Eruption and Commensal Skin Microbiota

Project description:EGFR targeted anti-cancer therapy induces severe skin toxicities, which affect life quality in patients. The lack of mechanistic details underlying these adverse events hampers their effective management. Here we identified EGFR as the epidermal master-regulator of the ERK pathway, which secures skin barrier integrity upon hair eruption. EGFR deficient epidermis displays a Th2-dominated expression signature and is permissive for excessive microbiota outgrowth. In the absence of EGFR, opening of the follicular ostia during hair eruption allows invasion of commensal microbiota aggravating barrier disruption and initiating an additional Th1 and Th17 response. Chronic folliculitis leads to Staphylococcus aureus dominated dysbiosis, further exacerbating inflammation and expanding barrier defects. Restoration of epidermal ERK signaling via therapeutic FGF7 treatment or transgenic SOS expression rescues skin barrier integrity in the absence of EGFR. These data reveal a gatekeeper function of the EGFR/ERK cascade in hair follicles securing the epidermal barrier around the erupting hair shaft.

2019-12-31 | GSE119376 | GEO

Commensal Microbiota Regulates Skin Barrier Function And Repair Via Signaling Through The Aryl Hydrocarbon Receptor

Project description:Essential to terrestrial life is the formation of a competent skin barrier that prevents desiccation and entry by harmful substances. A tightly orchestrated series of cellular changes is required for the proper formation of the epidermal permeability barrier. These changes occur in the context of the commensal skin microbiota. Using germ free mice and antibiotic depletion models, we demonstrate the microbiota is necessary for proper differentiation and repair of the barrier. These effects were mediated by keratinocyte signaling through the aryl hydrocarbon receptor (AHR), a xenobiotic receptor that also regulates epidermal differentiation. Murine skin lacking keratinocyte AHR was more susceptible to infection by S. aureus and increased pathology in a model of atopic dermatitis. Topical colonization with a defined consortium of human skin commensals restored barrier competence in germ free skin and during epicutaneous sensitization; these effects were dependent on keratinocyte AHR. We reveal a fundamental role for the commensal skin microbiota in directing skin barrier formation and repair through the AHR, with far-reaching implications for the numerous skin disorders characterized by disrupted epidermal differentiation and/or barrier competence.

2021-03-31 | GSE162925 | GEO

The ubiquitous human skin commensal Staphylococcus hominis protects against opportunistic pathogens

Project description:Staphylococcus hominis is frequently isolated from human skin and we hypothesize that it may protect the cutaneous barrier from opportunistic pathogens. We determined that S. hominis makes six unique auto inducing peptide (AIP) signals that inhibit the major virulence factor accessory gene regulator (agr) quorum sensing system of Staphylococcus aureus. We solved and confirmed the structures of three novel AIP signals in conditioned media by mass spectrometry, then validated synthetic AIP activity against all S. aureus agr classes. Synthetic AIPs also inhibited the conserved agr system in a related species, Staphylococcus epidermidis. We determined the distribution of S. hominis agr types on healthy human skin and found S. hominis agr-I and agr-II were highly represented across subjects. Further, synthetic AIP-II was protective in vivo against S. aureus-associated dermonecrotic or epicutaneous injury. Together, these findings demonstrate that a ubiquitous colonizer of human skin has a fundamentally protective role against opportunistic damage.

2022-04-04 | GSE199818 | GEO

Host cellular and immune responses in models of inflammatory skin conditions

Project description:Skin colonisation of varied communities of commensal microorganisms, such as Staphylococcus aureus (SA), Staphylococcus epidermidis (SE) and Staphylococcus capitis (SC) form the microbiome; a necessity for healthy skin. The skin changes characteristic of atopic dermatitis, a common inflammatory skin disease, have been shown to provide a favourable niche for SA colonisation. We utilised a reconstructed human epidermal (RHE) model recapitulating the stratified anatomy of the epidermis on which to test host responses to bacterial colonisation. SA proliferation was significantly inhibited in contrast to that seen with SE at both high and low colonisation loads after 24 hours. These data strongly suggest species specific regulation of staphylococcal growth, which is partially mediated by interaction with the epidermis.

2023-01-16 | GSE192454 | GEO

Skin cancer-associated S. aureus downregulates DNA repair mechanisms, and promotes oxidative stress and DNA damage in human keratinocytes

Project description:Actinic keratoses (AK) are premalignant lesions common on photo-damaged skin that, over time, can progress to squamous cell carcinoma (SCC). A high bacterial load of Staphylococcus aureus is associated with AK and SCC but it is unknown whether this has a direct impact on skin cancer development. To determine whether S. aureus is able to trigger pro-tumorigenic skin responses, we performed RNAseq and shotgun proteomics on primary human keratinocytes after challenge with sterile culture supernatant (‘secretome’) from S. aureus clinical strains isolated from AK and SCC. Certain S. aureus secretomes induced keratinocytes to overexpress SCC biomarkers that have been associated with skin carcinogenesis, and upregulate the expression of enzymes linked with reduced skin barrier function. Further, S. aureus secretomes downregulated DNA repair mechanisms and induced oxidative stress markers. Subsequent experiments confirmed that exposure to SCC-derived S. aureus secretomes lead to increased intracellular ROS levels and DNA damage in primary human keratinocytes. Altogether, this study reveal a novel mechanism for the pro-tumorigenic activity of S. aureus. Further studies are required to determine whether S. aureus products promote SCC development in vivo, which would have important implications for the treatment of AK and prevention of SCC.

2022-05-17 | PXD031676 | panorama

Barrier formation by primary human airway epithelial cells sets limits to Staphylococcus aureus adhesion, invasion and cytotoxicity

Project description:Barrier formation by primary human airway epithelial cells sets limits to Staphylococcus aureus adhesion, invasion and cytotoxicity

2025-01-07 | GSE285788 | GEO

Skin cancer-associated S. aureus downregulates DNA repair mechanisms, and promotes oxidative stress and DNA damage in human keratinocytes

2022-05-11 | PXD031622 | Pride

RNA sequencing of whole skin from neonatal mice colonized with Staphlyococcus epidermidis versus Staphylococcus aureus

Project description:RNA sequencing of whole skin from neonatal mice colonized with Staphlyococcus epidermidis versus Staphylococcus aureus

2019-11-11 | GSE130986 | GEO

RNA sequencing of Tregs from skin of neonatal mice colonized with Staphlyococcus epidermidis versus Staphylococcus aureus

Project description:RNA sequencing of Tregs from skin of neonatal mice colonized with Staphlyococcus epidermidis versus Staphylococcus aureus

2019-11-11 | GSE130984 | GEO

Bacterial membrane phosphatidylglycerols activate a population of human CD1a-restricted t cells

Project description:Expressed on epidermal Langerhans cells, CD1a presents a range of self-lipid antigens found within the skin. However, the extent to which CD1a presents microbial ligands from skin bacteria is unclear. Here, we identified CD1a-dependent T cell responses to phosphatidylglycerol (PG), a ubiquitous bacterial membrane phospholipid, as well as to lysyl phosphatidylglycerol (lysylPG), a modified PG, present in the many gram positive bacteria, and highly abundant in Staphylococcus aureus. Specifically, PG and lysylPG together constitute the vast majority of the structural membrane lipids in Staphylococcus aureus. The crystal structure of the CD1a-lysylPG complex showed that the acyl chains were buried within the A′- and F′-pockets of CD1a, while the lysine-modified phosphoglycerol headgroup protruded from the F′-portal and was available for T cell receptor contact. Using lysylPG-loaded CD1a tetramers, we identified T cells in peripheral blood and in skin that respond to this lipid in a dose dependent manner. Tetramer+ CD4+ T cell lines secreted Th2 cytokines in response to lysylPG as well as to co-cultures of CD1a+ dendritic cells and Staphylococcus aureus. The expansion of CD4+ CD1a-lysylPG tetramer+ T cells in atopic dermatitis patients, indicates a response to a lipid made by bacteria associated with atopic dermatitis, and provide a link supporting involvement of PG-based lipid-specific T cells in the pathogenesis of dermatitis.

2022-12-19 | GSE186459 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data